Therapeutic relevance of AT2 receptors in cardiovascular disease and aging

肾素血管紧张素系统的药理调节是循证心血管治疗的基石。然而，它们的分子机制还不完全清楚，一些治疗方案还没有被充分利用。荷尔蒙血管紧张素II通过不同的结合部位引起兴奋和抑制心血管效应。对当代社会来说，特别重要的是人口结构向老龄化人口的转变。2002年，澳大利亚有13%的人口(约250万)年龄在65岁或以上，据估计，到2021年，这一数字将增加到18%(约400万)。虽然血脂状况和吸烟是众所周知的心血管疾病风险因素，但到目前为止，高龄是心血管疾病的最大风险因素。在此背景下，我们发现抑制性血管紧张素II结合部位在衰老中发挥更大的作用，这可能是由于血管紧张素II的分解产物具有自己独特的作用。该项目将确定各种血管紧张素产品和可能起类似作用的新化合物在老年高血压人群中改善血管张力和逆转心血管疾病的相对作用。

Pharmacological modulation of the renin angiotensin system is a cornerstone of evidence-based cardiovascular therapeutics. However, their molecular mechanisms are not entirely clear and some therapeutic options have not been utilized to their full potential. The hormone angiotensin II causes both excitatory and inhibitory cardiovascular effects via distinct binding sites. Of particular importance to contemporary society is the shift in the demographic to a more aged population. In Australia in 2002, 13% of the population (~2.5 million) were aged 65 years or over, and it has been estimated that this number will increase to 18% (~4 million) by the year 2021. While lipid status and smoking are well known risk factors for cardiovascular disease, advanced age by far confers the greatest risk for cardiovascular disease. In this context, we have found a greater role of the inhibitory angiotensin II binding site in aging that may result from breakdown products of angiotensin II having their own unique effects. This project will determine the relative role of various angiotensin products, and novel compounds that may act similarly, to improve vascular tone and reverse cardiovascular disease in the elderly, hypertensive population.